Response systems

2012 senior Scholar Award in aging

Animals are tough. Their developmental processes and physiological regulatory mechanisms are astonishingly robust despite the slings and arrows of environmental contingencies, including changing temperature, food availability, and pathogen infection. The nematode C. elegans exemplifies... >> MORE

2012 senior Scholar Award in aging

C. elegans research has made profound contributions to the fields of aging, health and disease. In particular, genetic analysis in C. elegans has identified components of major signaling pathways that underlie diseases of aging such as cancer and Alzheimer's disease, and revealed... >> MORE

2012 senior Scholar Award in aging

The use of simple model organisms for aging such as yeast, worms and flies has driven the aging field forward and been instrumental for the identification of cellular pathways that modulate the aging process. From work in my lab and many others, a set of conserved aging genes have been... >> MORE

2012 senior Scholar Award in aging

The literature on aging includes very many papers correlating changes in chromatin structure with aging, including in yeast and mammalian cells. A limitation of these studies is that, until recently, we have had no clear picture of how chromatin architecture is related to gene regulation in... >> MORE

2011 senior Scholar Award in aging

Human aging incorporates multiple changes throughout the body such as slower metabolism and loss of muscle. Aging is also associated with a reduced aerobic capacity as a result of reduced lung function, poorer blood circulation, decreased cardiac output, and limited exercise capacity. These age-... >> MORE

2011 senior Scholar Award in aging

Proteins must achieve their correct three-dimensional folded structure in order to carry out their cellular functions. Failure to fold its proteins can be catastrophic for cells, since misfolded proteins can aggregate into toxic amyloid species. Aging is universally associated with a decline in... >> MORE

2011 senior Scholar Award in aging

The overall purpose of the work in our laboratory is to demonstrate that there is a hormonal regulation of organismal aging. This work is based on the observed effect of the bone-derived hormone osteocalcin in favoring glucose homeostasis, energy expenditure and male fertility. These three... >> MORE

2011 senior Scholar Award in aging

The overall goal of this project will be to test our hypothesis that stimulating anabolic pathways in skeletal muscle may lead to extension of life span. Specifically, we will examine the effect of blocking the myostatin signaling pathway on longevity in mice. We discovered myostatin as a... >> MORE

2011 senior Scholar Award in aging

Muscle fatigue is one of the most fundamental physiological processes. Fatigue of skeletal muscle determines the outer limits of physical activity and explains, for example, why an elite athlete who can run 100 meters in under 10 seconds cannot run 1,000 meters in 100 seconds. Severe muscle... >> MORE

2011 senior Scholar Award in aging

Aging and stress, stress and aging - a pair of ominous conditions that can affect the quality of life. When events go awry, the cellular machinery senses molecular damage and compensates by induction of protective cellular stress responses. Aging, however, compromises the robustness of these... >> MORE

2011 senior Scholar Award in aging

The p53 protein is a prominent tumor suppressor, often referred to as the “guardian of the genome”. p53 is stabilized and activated in response to a variety of stress signals and, in turn, activates specific target genes through its function as a conventional transcription factor that binds to... >> MORE

2011 senior Scholar Award in aging

The overall goal of our application is to initiate a novel series of studies that demonstrate a role for the hypothalamus in regulation of aging and age-related disease. Several studies suggest that hypothalamic mechanisms regulate aspects of aging in both invertebrates and vertebrates but their... >> MORE

2011 senior Scholar Award in aging

We are interested in determining the mechanisms underlying age-related declines in tissue homeostasis and repair. Following embryogenesis, most animals undergo a dramatic period of growth, during which the body, and all its component parts, increase in size and mass. On reaching adulthood, net... >> MORE

2010 senior Scholar Award in aging
The nematode C. elegans has proven to be an invaluable model organism for identifying mechanisms that influence longevity, and may be conserved across species. Recently considerable interest has been focused on how aging is influenced by the target of rapamycin (TOR) signaling pathway. TOR... >> MORE
2010 senior Scholar Award in aging
We have developed two new model systems that lead to significant increases in mouse maximal longevity. One uses a "Crowded Litter" (CL) approach to reduce food availability, but only in the first 3 weeks of life. The other involves genetic ablation of the gene for MIF, a pro-inflammatory cytokine... >> MORE
2010 senior Scholar Award in aging

With the support of this award we will apply two "Next Generation" approaches to the study of genetic mouse models in which specific steps of TORC1 signaling (i.e., via the mTOR/raptor complex itself or the downstream proteins 4EBP1 and S6K1) are selectively altered in key young and... >> MORE

2009 senior Scholar Award in aging

Mitochondria are cellular organelles that use the oxygen we breathe to oxidize carbohydrates, fats and proteins. The oxygen is fully reduced to form water, and energy is released. The mitochondria capture this energy to phosphorylate ADP to ATP, a molecule that can be hydrolyzed by the cells to... >> MORE

2009 senior Scholar Award in aging
The long-term objective of our laboratory is to understand the beneficial relationship between hormones and the aging process. Of particular interest is the pituitary hormone, growth hormone, and itís role in metabolism and stress resistance in aging. Our lab has helped to establish a compelling... >> MORE
2009 senior Scholar Award in aging
We will employ bdelloid rotifers, a group of small, entirely female freshwater invertebrates, as a new, particularly advantageous model system for investigating the processes responsible for aging -- the increase of mortality with increasing age. Initially, we will employ bdelloid rotifers to test... >> MORE
2009 senior Scholar Award in aging

Genome damage caused by reactive oxygen species has long been though to be associated with aging and neurodegeneration. Because of limitations in available experimental methods, previous work focused on determining the overall levels of various kinds of oxidative damage. It is likely, though,... >> MORE

2009 senior Scholar Award in aging
This proposal is to study the role of RIP1 kinase and its signaling pathway in mediating production of an important pro-inflammatory cytokine, TNFα, and its implication in aging. Increased levels of TNFα during aging are detrimental for longevity by contributing to the pathogenesis of... >> MORE
2008 senior Scholar Award in aging
Oxidative stress has been implicated in the aging process and in the development of many age-related diseases including cancer. My laboratory has focused on studies of a critical consequence of oxidative stress: oxidative damage to DNA. When DNA is oxidized and not properly repaired, mutations and... >> MORE
2008 senior Scholar Award in aging
Every day our body must defend itself against countless foreign substances termed xenobiotics. Many of these substances are harmful and over time repeated exposures can damage the body and accelerate the aging process. Our ability to break down and excrete these foreign substances may be one of... >> MORE
2008 senior Scholar Award in aging

Aging is no less than war waged between chemistry and biochemistry. Chemical reactions result in widespread spontaneous damage to the biomolecules essential for life. However, biochemical reactions can limit or even reverse this damage. Understanding the ability of organisms to mount... >> MORE

2008 senior Scholar Award in aging
Our laboratory works with an enzyme called PI3 kinase (PI3K). This enzyme has a long history, having first been discovered in the 1980s due to its role in cancer. We now know that PI3K plays a number of important roles in individual cells and in the physiology of the whole organism. For instance... >> MORE
2008 senior Scholar Award in aging
There is a great deal of evidence indicating that microglial cell dysfunction plays a role in a variety of neurodegenerative diseases associated with aging, including Alzheimer's, Multiple Sclerosis, Parkinson's Disease and Stroke. Microglia make up approximately 10% of the cells in the brain. They... >> MORE
2008 senior Scholar Award in aging
We investigate the molecular basis of insulin-like signaling to understand the pathophysiology of metabolic disease that progresses to diabetes and its related disordersóincluding obesity and infertility; cardiovascular; retinal disease; and the regulation of life-span. Our studies reveal common... >> MORE
2007 senior Scholar Award in aging
Precursor cells that continuously regenerate are vital for health. In order to cure or postpone age-related functional deterioration and disease, it is necessary to identify which precursor cells regulate the rates of aging in various biological systems. Dr. Harrison and his associates are... >> MORE
2007 senior Scholar Award in aging
While many factors contribute to longevity, studies over the last decade have revealed particularly important roles for the activity of the insulin and IGF-1 signaling systems. Indeed, these signaling systems have been shown to play a role in control of lifespan in organisms as diverse as worms,... >> MORE
2007 senior Scholar Award in aging
Substantial epidemiological evidence indicates that conditions in utero program the susceptibility to age-related diseases, in particular atherosclerosis, the underlying cause of most heart attacks and strokes. However, little is known about maternal factors responsible for such... >> MORE
2006 senior Scholar Award in aging
Decreased insulin-like growth factor (IGF)-I signaling is associated with extended lifespan. However, the underlying mechanisms relating the IGF system and longevity are poorly understood. The IGF system is complex with ubiquitous IGF receptors present on cells to transduce a response, but also... >> MORE
2006 senior Scholar Award in aging
The discovery of genes that positively or negatively affect how long an organism lives has been a tremendous advance in the science of aging. While numerous genes have been isolated that affect the longevity of organisms like worms and flies, to date, there have been relatively few genes that... >> MORE
2006 senior Scholar Award in aging
A consequence of normal cellular respiration is the formation of reactive oxygen species, small molecules that can react with a variety of cellular components. Many studies have suggested that the interaction of reactive oxygen species with cellular structures contributes to aging and... >> MORE
2005 senior Scholar Award in aging

We are interested in identifying drugs that can delay human aging and extend human lifespan. Such drugs might have beneficial uses, and the analysis of how such drugs work could provide important insights into the regulation of aging. As a first step, we tested whether drugs that are approved... >> MORE

2005 senior Scholar Award in aging

My laboratory has been focused on elucidating the function of the Klotho gene. The Klotho gene was originally identified as a gene mutated in a mouse strain that exhibits a syndrome resembling human aging, including a shortened lifespan, skin atrophy, muscle atrophy, neuronal... >> MORE

2005 senior Scholar Award in aging

Life-long dietary restriction can delay age-related impairments and extend lifespan. However, life-long dietary restriction itself would not be a practical intervention in humans. Therefore many investigators are studying the mechanism by which dietary restriction produces its beneficial... >> MORE

2005 senior Scholar Award in aging

For unknown reasons, individuals with the metabolic syndrome frequently have high blood pressure, increased blood lipids, reduced exercise capacity, oxidative stress, increased inflammation, glucose intolerance (diabetes), premature cardiovascular disease (atherosclerosis, heart attack and... >> MORE

2005 senior Scholar Award in aging

Overview. Living in an aerobic world, oxidative stress has been implicated in the aging process and in the development of a number of age-related, neurological diseases. An organism, however, has means to detoxify reactive oxygen species, including the enzymes glutathione peroxidase,... >> MORE

2004 senior Scholar Award in aging

The goal of these studies is to clarify the molecular mechanisms for two prominent features of aged organisms: 1) the accumulation of abnormal proteins in cells, and 2) the marked, debilitating loss of muscle mass (sarcopenia). To understand these phenomena, we shall build upon recent advances... >> MORE

2004 senior Scholar Award in aging

Epigenetics entails the study of the switching on and off of genes during development, cell proliferation and also by environmental insults. Epigenetic changes can result in the stable inheritance of a given spectrum of gene activities in specific cells. Genome modifications resulting from... >> MORE

2004 senior Scholar Award in aging

The work by my laboratory at the California Institute of Technology is about understanding bits and pieces of the following large problem: how and why cells destroy their own proteins? A related problem is to understand the consequences of having protein destruction machines in every cell of... >> MORE

2003 senior Scholar Award in aging

We are studying effects of genes and hormones on aging. We have shown that mutant mice with inherited deficiency of several pituitary hormones live much longer than their normal siblings. These mutants, the Ames dwarf mice, maintain their health, learning abilities, and memory until late in life... >> MORE

2003 senior Scholar Award in aging

One of the most widely accepted theories in aging research is the free radical or oxidative stress theory of aging, which states that a steady-state accumulation of oxidative damage in cells and tissues leads to aging. Over the past two decades, it has been shown that oxidative damage to cells... >> MORE

2002 senior Scholar Award in aging

A decline in the capacity of living organisms to respond vigorously to external stresses (elevated temperature, damaging radiation, reactive chemical agents, etc.) and to maintain homeostasis is a hallmark of aging and is largely responsible for the age-related increase in mortality.... >> MORE

2002 senior Scholar Award in aging

During the last decade, remarkable discoveries in the small roundworm C. elegans have shown that aging is regulated hormonally by a regulatory system similar to that of the human insulin and IGF-1 (insulin-like growth factor) endocrine systems. This same endocrine system governs the aging... >> MORE

2002 senior Scholar Award in aging

Hypothesis: Small molecule pharmacological agents, including synthetic hormones, that enhance stress response will slow aging and age-related functional decline.

Much of the remarkable progress in the biology of aging has emerged from the lifespan extension paradigm in simple animal... >> MORE

2001 senior Scholar Award in aging

Caloric restriction extends life-span in a wide variety of eukaryotic organisms from yeast to mammals. Cellular responses to nutritional availability are mediated by the cAMP signaling pathway in bacteria, cyanobacteria, and unicellular eukaryotes, and Dr. Guarente and co-workers demonstrated... >> MORE

2001 senior Scholar Award in aging

Generalized aging at the cellular level is thought to arise from the accumulation of damage to protein and nucleic acids that eventually results in the impairment of normal cellular function or transformation of the cells to a cancerous form of growth. How does this damage occur? One hypothesis... >> MORE

2001 senior Scholar Award in aging

Estrogen appears to protect the aging brain against cognitive dysfunction, neurodegenerative diseases, and brain injury such as stroke. The menopause is accompanied by a dramatic and permanent decrease in estrogen levels. During the past century, the longevity of women has increased from 50 to... >> MORE

2000 senior Scholar Award in aging

The present proposal is aimed at testing the hypothesis that activation of brain specific Uncoupling Proteins (UCPs) could prove chronically neuroprotective by providing a combination of two protective measures a) reducing free radical formation, b) reducing the vulnerability of mitochondria to... >> MORE

2000 senior Scholar Award in aging

Proteins make up a substantial portion of the cell's mass and are involved in most regulated aspects of its activity. They consist of complex polymers of amino acids joined together through peptide bonds. To function, proteins must undergo a folding process that gives them the proper three... >> MORE

1999 senior Scholar Award in aging

Evidence that oxidative damage, a by-product of normal metabolism in virtually all animals, is causally involved in the process of aging and the development of degenerative disease has been steadily accumulating for more than forty years. An understanding of the exact nature of this damage to... >> MORE

1999 senior Scholar Award in aging

Few mammalian models of aging have the phenotype of increased life span. Virtually all work has focused on food restricted (FR) rodents. Although many changes in physiologic function and gene expression have been identified, it is difficult to determine which changes contribute... >> MORE

1999 senior Scholar Award in aging

We propose to study the importance of a cellular signaling pathway, termed the P13K/Akt/Daf16 pathway, for determining the life span of cells and multi-cellular organisms. Disruption of the P13K/Akt pathway has previously been shown to affect the life span of the invertebrate organism C. ... >> MORE

2013 new Scholar Award in aging

Hormonal signals released by neurons affect our moods, emotions, and appetites. As a consequence, mood disorders such as schizophrenia and depression, and metabolic disorders such as obesity and diabetes can be caused by defects in neuronal hormone release. Many of these disorders have an age-... >> MORE

2013 new Scholar Award in aging

The progressive loss of skeletal muscle function and mass (sarcopenia) is a serious feature of aging and a key component of the geriatric syndrome of frailty. Epidemiological surveys in humans indicate that muscle aging influences the progression of several age-related diseases in other tissues... >> MORE

2013 new Scholar Award in aging

Dietary restriction and the modulation of nutrient-sensing pathways are robust and reproducible interventions that extend life/healthspan in model organisms. Accordingly, the mitochondrion, being the single most important metabolic organelle, receives much attention as a major contributor to... >> MORE

2013 new Scholar Award in aging

Dietary restriction increases lifespan and slows aging-related decline in health across species. Altered control of gene expression at the level of protein synthesis has emerged as an important but ill-defined player in this process. The importance of understanding the connection between... >> MORE

2012 new Scholar Award in aging

The Ghazi lab uses Caenorhabditis elegans as a model to understand the genetic mechanisms that influence how long animals live and how they age. We are particularly interested in the relationship between aging and reproduction, two fundamental aspects of our lives.

Traditionally... >> MORE

2012 new Scholar Award in aging

Aging is associated with gradual functional decline of many organs and systems within our bodies. The specific manifestations of aging vary among different tissues, and common biological mechanisms driving natural aging progression have not been established. We aim to examine a key aspect of... >> MORE

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